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https://www.readbyqxmd.com/read/28535374/discovery-of-stromal-regulatory-networks-that-suppress-ras-sensitized-epithelial-cell-proliferation
#1
Huayang Liu, James A Dowdle, Safiya Khurshid, Nicholas J Sullivan, Nicholas Bertos, Komal Rambani, Markus Mair, Piotr Daniel, Esther Wheeler, Xing Tang, Kyle Toth, Michael Lause, Markus E Harrigan, Karl Eiring, Connor Sullivan, Matthew J Sullivan, Serena W Chang, Siddhant Srivastava, Joseph S Conway, Raleigh Kladney, Joseph McElroy, Sooin Bae, Yuanzhi Lu, Ali Tofigh, Sadiq M I Saleh, Soledad A Fernandez, Jeffrey D Parvin, Vincenzo Coppola, Erin R Macrae, Sarmila Majumder, Charles L Shapiro, Lisa D Yee, Bhuvaneswari Ramaswamy, Michael Hallett, Michael C Ostrowski, Morag Park, Helen M Chamberlin, Gustavo Leone
Mesodermal cells signal to neighboring epithelial cells to modulate their proliferation in both normal and disease states. We adapted a Caenorhabditis elegans organogenesis model to enable a genome-wide mesodermal-specific RNAi screen and discovered 39 factors in mesodermal cells that suppress the proliferation of adjacent Ras pathway-sensitized epithelial cells. These candidates encode components of protein complexes and signaling pathways that converge on the control of chromatin dynamics, cytoplasmic polyadenylation, and translation...
May 22, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28535307/intergenerational-impact-of-paternal-lifetime-exposures-to-both-folic-acid-deficiency-and-supplementation-on-reproductive-outcomes-and-imprinted-gene-methylation
#2
Lundi Ly, Donovan Chan, Mahmoud Aarabi, Mylène Landry, Nathalie A Behan, Amanda J MacFarlane, Jacquetta Trasler
STUDY QUESTION: Do paternal exposures to folic acid deficient (FD), and/or folic acid supplemented (FS) diets, throughout germ cell development adversely affect male germ cells and consequently offspring health outcomes? SUMMARY ANSWER: Male mice exposed over their lifetimes to both FD and FS diets showed decreased sperm counts and altered imprinted gene methylation with evidence of transmission of adverse effects to the offspring, including increased postnatal-preweaning mortality and variability in imprinted gene methylation...
May 23, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28535255/tea-and-coffee-consumption-in-relation-to-dna-methylation-in-four-european-cohorts
#3
Weronica E Ek, Elmar W Tobi, Muhammad Ahsan, Erik Lampa, Erica Ponzi, Soterios A Kyrtopoulos, Panagiotis Georgiadis, L H Lumey, Bastiaan T Heijmans, Maria Botsivali, Ingvar A Bergdahl, Torgny Karlsson, Mathias Rask-Andersen, Domenico Palli, Erik Ingelsson, Åsa K Hedman, Lena M Nilsson, Paolo Vineis, Lars Lind, James M Flanagan, Åsa Johansson
Lifestyle factors, such as food choices and exposure to chemicals, can alter DNA methylation and lead to changes in gene activity. Two such exposures with pharmacologically active components are coffee and tea consumption. Both coffee and tea has been suggested to play an important role in modulating disease-risk in humans by suppressing tumour progression, decreasing inflammation and influencing estrogen metabolism. These mechanisms may be mediated by changes in DNA methylation.To investigate if DNA methylation in blood is associated with coffee and tea consumption we performed a genome-wide DNA methylation study for coffee and tea consumption in four European cohorts (N = 3,096)...
May 23, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28535251/mms1-binds-to-g-rich-regions-in-saccharomyces-cerevisiae-and-influences-replication-and-genome-stability
#4
Katharina Wanzek, Eike Schwindt, John A Capra, Katrin Paeschke
The regulation of replication is essential to preserve genome integrity. Mms1 is part of the E3 ubiquitin ligase complex that is linked to replication fork progression. By identifying Mms1 binding sites genome-wide in Saccharomyces cerevisiae we connected Mms1 function to genome integrity and replication fork progression at particular G-rich motifs. This motif can form G-quadruplex (G4) structures in vitro. G4 are stable DNA structures that are known to impede replication fork progression. In the absence of Mms1, genome stability is at risk at these G-rich/G4 regions as demonstrated by gross chromosomal rearrangement assays...
May 23, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28534927/genome-wide-association-study-for-birth-weaning-and-yearling-weight-in-colombian-brahman-cattle
#5
Rodrigo Martínez, Diego Bejarano, Yolanda Gómez, Romain Dasoneville, Ariel Jiménez, Gael Even, Johann Sölkner, Gabor Mészáros
Genotypic and phenotypic data of 1,562 animals were analyzed to find genomic regions that potentially influence the birth weight (BW), weaning weight at seven months of age (WW) and yearling weight (YW) of Colombian Brahman cattle, with genotyping conducted using Illumina Bead chip array with 74,669 SNPs. A Single Step Genomic BLUP (ssGBLP), approach was used to estimate the proportion of variance explained by each marker. Multiple regions scattered across the genome were found to influence weights at different ages, also dependent on the trait component (direct or maternal)...
May 22, 2017: Genetics and Molecular Biology
https://www.readbyqxmd.com/read/28534526/impact-of-genetic-polymorphisms-determining-leukocyte-neutrophil-count-on-chemotherapy-toxicity
#6
S J Glisovic, Y D Pastore, V Gagne, M Plesa, C Laverdière, J M Leclerc, D Sinnett, M Krajinovic
Neutropenia and infection are major dose-limiting side effects of chemotherapy. The risk of initial infection and subsequent complications are directly related to the depth and duration of neutropenia. Recent genome-wide association studies identified variants in DARC and CXCL2 genes, and in ORMDL3-GSDMA-CSF3 locus on chromosome 17q21 that influence white blood cell and neutrophil counts in healthy individuals. To investigate whether polymorphisms in these loci in conjunction with chemotherapy may modulate risk of treatment complications, we analyzed 21 SNPs across these genes for an association with chemotherapy-related neutropenia and infection in 286 Caucasian children with acute lymphoblastic leukemia...
May 23, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28534508/utx-promotes-hormonally-responsive-breast-carcinogenesis-through-feed-forward-transcription-regulation-with-estrogen-receptor
#7
G Xie, X Liu, Y Zhang, W Li, S Liu, Z Chen, B Xu, J Yang, L He, Z Zhang, T Jin, X Yi, L Sun, Y Shang, J Liang
UTX is implicated in embryonic development and lineage specification. However, how this X-linked histone demethylase contributes to the occurrence and progression of breast cancer remains to be clarified. Here we report that UTX is physically associated with estrogen receptor (ER) and functions in ER-regulated transcription. We showed that UTX coordinates with JHDM1D and CBP to direct H3K27 methylation-acetylation transition and to create a permissive chromatin state on ER targets. Genome-wide analysis of the transcriptional targets of UTX by ChIP-seq identified a set of genes such as chemokine receptor CXCR4 that are intimately involved in breast cancer tumorigenesis and metastasis...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28534505/proteomic-identification-of-erp29-as-a-key-chemoresistant-factor-activated-by-the-aggregating-p53-mutant-arg282trp
#8
Y Zhang, Y Hu, J-L Wang, H Yao, H Wang, L Liang, C Li, H Shi, Y Chen, J-Y Fang, J Xu
Mutation of the TP53 gene represents a prevalent genetic alteration in human cancers, and a subset of p53 mutants may form amyloid-like aggregates that contribute to the gain of oncogenic functions (GOFs) and chemoresistance. Here we identify the pathways that may mediate the aggregation-associated GOF by using combined proteomic analysis and genome-wide recruitment profiling. Mass spectrometry revealed activation of unfolded protein response (UPR) pathway and upregulation of endoplasmic reticulum protein 29 (ERp29) in (R282W)TP53-expressing cells that were exposed to cisplatin stress...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28534485/pseudoexfoliation-syndrome-associated-genetic-variants-affect-transcription-factor-binding-and-alternative-splicing-of-loxl1
#9
Francesca Pasutto, Matthias Zenkel, Ursula Hoja, Daniel Berner, Steffen Uebe, Fulvia Ferrazzi, Johannes Schödel, Panah Liravi, Mineo Ozaki, Daniela Paoli, Paolo Frezzotti, Takanori Mizoguchi, Satoko Nakano, Toshiaki Kubota, Shinichi Manabe, Erika Salvi, Paolo Manunta, Daniele Cusi, Christian Gieger, Heinz-Erich Wichmann, Tin Aung, Chiea Chuen Khor, Friedrich E Kruse, André Reis, Ursula Schlötzer-Schrehardt
Although lysyl oxidase-like 1 (LOXL1) is known as the principal genetic risk factor for pseudoexfoliation (PEX) syndrome, a major cause of glaucoma and cardiovascular complications, no functional variants have been identified to date. Here, we conduct a genome-wide association scan on 771 German PEX patients and 1,350 controls, followed by independent testing of associated variants in Italian and Japanese data sets. We focus on a 3.5-kb four-component polymorphic locus positioned spanning introns 1 and 2 of LOXL1 with enhancer-like chromatin features...
May 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28534453/serotonin-functioning-and-adolescents-alcohol-use-a-genetically-informed-study-examining-mechanisms-of-risk
#10
Frances L Wang, Laurie Chassin, John E Bates, Danielle Dick, Jennifer E Lansford, Gregory S Pettit, Kenneth A Dodge
The current study used data from two longitudinal samples to test whether self-regulation, depressive symptoms, and aggression/antisociality were mediators in the relation between a polygenic score indexing serotonin (5-HT) functioning and alcohol use in adolescence. The results from an independent genome-wide association study of 5-hydroxyindoleacetic acid in the cerebrospinal fluid were used to create 5-HT polygenic risk scores. Adolescents and/or parents reported on adolescents' self-regulation (Time 1), depressive symptoms (Time 2), aggression/antisociality (Time 2), and alcohol use (Time 3)...
May 23, 2017: Development and Psychopathology
https://www.readbyqxmd.com/read/28534241/a-genetic-variant-in-fign-gene-reduces-the-risk-of-congenital-heart-disease-in-han-chinese-populations
#11
Dan Wang, Maoping Chu, Feng Wang, Aihua Zhou, Miaohua Ruan, Yiming Chen
Congenital heart disease (CHD) is one of the most common birth anomalies worldwide. Folate deficiency is an independent risk factor for CHD. Genome-wide association studies (GWAS) revealed that human folate level could be significantly influenced by fidgetin (FIGN), methylenetetrahydrofolate reductase (MTHFR), prickle homolog 2 (PRICKLE2), synaptotagmin 9 (SYT9), gamma-aminobutyric acid B receptor 2 (GABBR2), and alkaline phosphatase (ALPL) genes. The association between the above-mentioned six variants and CHD was examined in the two independent case-control studies in a total of 868 CHD patients and 931 healthy controls...
May 22, 2017: Pediatric Cardiology
https://www.readbyqxmd.com/read/28534238/a-fast-algorithm-for-bayesian-multi-locus-model-in-genome-wide-association-studies
#12
Weiwei Duan, Yang Zhao, Yongyue Wei, Sheng Yang, Jianling Bai, Sipeng Shen, Mulong Du, Lihong Huang, Zhibin Hu, Feng Chen
Genome-wide association studies (GWAS) have identified a large amount of single-nucleotide polymorphisms (SNPs) associated with complex traits. A recently developed linear mixed model for estimating heritability by simultaneously fitting all SNPs suggests that common variants can explain a substantial fraction of heritability, which hints at the low power of single variant analysis typically used in GWAS. Consequently, many multi-locus shrinkage models have been proposed under a Bayesian framework. However, most use Markov Chain Monte Carlo (MCMC) algorithm, which are time-consuming and challenging to apply to GWAS data...
May 22, 2017: Molecular Genetics and Genomics: MGG
https://www.readbyqxmd.com/read/28534127/genetics-of-triglycerides-and-the-risk-of-atherosclerosis
#13
REVIEW
Jacqueline S Dron, Robert A Hegele
PURPOSE OF REVIEW: Plasma triglycerides are routinely measured with a lipid profile, and elevated plasma triglycerides are commonly encountered in the clinic. The confounded nature of this trait, which is correlated with numerous other metabolic perturbations, including depressed high-density lipoprotein cholesterol (HDL-C), has thwarted efforts to directly implicate triglycerides as causal in atherogenesis. Human genetic approaches involving large-scale populations and high-throughput genomic assessment under a Mendelian randomization framework have undertaken to sort out questions of causality...
July 2017: Current Atherosclerosis Reports
https://www.readbyqxmd.com/read/28534096/genomic-prediction-ability-for-yield-related-traits-in-german-winter-barley-elite-material
#14
Patrick Thorwarth, Jutta Ahlemeyer, Anne-Marie Bochard, Kerstin Krumnacker, Hubert Blümel, Eberhard Laubach, Nadine Knöchel, László Cselényi, Frank Ordon, Karl J Schmid
Genomic prediction was evaluated in German winter barley breeding lines. In this material, prediction ability is strongly influenced by population structure and main determinant of prediction ability is the close genetic relatedness of the breeding material. To ensure breeding progress under changing environmental conditions the implementation and evaluation of new breeding methods is of crucial importance. Modern breeding approaches like genomic selection may significantly accelerate breeding progress. We assessed the potential of genomic prediction in a training population of 750 genotypes, consisting of multiple six-rowed winter barley (Hordeum vulgare L...
May 22, 2017: TAG. Theoretical and Applied Genetics. Theoretische und Angewandte Genetik
https://www.readbyqxmd.com/read/28533979/a-genome-wide-assessment-of-stages-of-elevational-parapatry-in-bornean-passerine-birds-reveals-no-introgression-implications-for-processes-and-patterns-of-speciation
#15
Robert G Moyle, Joseph D Manthey, Peter A Hosner, Mustafa Rahman, Maklarin Lakim, Frederick H Sheldon
Topographically complex regions often contain the close juxtaposition of closely related species along elevational gradients. The evolutionary causes of these elevational replacements, and thus the origin and maintenance of a large portion of species diversity along elevational gradients, are usually unclear because ecological differentiation along a gradient or secondary contact following allopatric diversification can produce the same pattern. We used reduced representation genomic sequencing to assess genetic relationships and gene flow between three parapatric pairs of closely related songbird taxa (Arachnothera spiderhunters, Chloropsis leafbirds, and Enicurus forktails) along an elevational gradient in Borneo...
2017: PeerJ
https://www.readbyqxmd.com/read/28533820/medip-seq-and-ncpg-analyses-illuminate-sexually-dimorphic-methylation-of-gonadal-development-genes-with-high-historic-methylation-in-turtle-hatchlings-with-temperature-dependent-sex-determination
#16
Srihari Radhakrishnan, Robert Literman, Beatriz Mizoguchi, Nicole Valenzuela
BACKGROUND: DNA methylation alters gene expression but not DNA sequence and mediates some cases of phenotypic plasticity. Temperature-dependent sex determination (TSD) epitomizes phenotypic plasticity where environmental temperature drives embryonic sexual fate, as occurs commonly in turtles. Importantly, the temperature-specific transcription of two genes underlying gonadal differentiation is known to be induced by differential methylation in TSD fish, turtle and alligator. Yet, how extensive is the link between DNA methylation and TSD remains unclear...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28533787/genome-wide-analysis-of-gene-expression-provides-new-insights-into-cold-responses-in-thellungiella-salsuginea
#17
Jiangshan Wang, Quan Zhang, Feng Cui, Lei Hou, Shuzhen Zhao, Han Xia, Jingjing Qiu, Tingting Li, Ye Zhang, Xingjun Wang, Chuanzhi Zhao
Low temperature is one of the major environmental stresses that affects plant growth and development, and leads to decrease in crop yield and quality. Thellungiella salsuginea (salt cress) exhibits high tolerance to chilling, is an appropriate model to investigate the molecular mechanisms of cold tolerance. Here, we compared transcription changes in the roots and leaves of T. salsuginea under cold stress using RNA-seq. We identified 2,782 and 1,430 differentially expressed genes (DEGs) in leaves and roots upon cold treatment, respectively...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28533738/genetics-of-tinnitus-still-in-its-infancy
#18
REVIEW
Barbara Vona, Indrajit Nanda, Wafaa Shehata-Dieler, Thomas Haaf
Tinnitus is the perception of a phantom sound that affects between 10 and 15% of the general population. Despite this considerable prevalence, treatments for tinnitus are presently lacking. Tinnitus exhibits a diverse array of recognized risk factors and extreme clinical heterogeneity. Furthermore, it can involve an unknown number of auditory and non-auditory networks and molecular pathways. This complex combination has hampered advancements in the field. The identification of specific genetic factors has been at the forefront of several research investigations in the past decade...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28533524/enhancing-the-genome-editing-toolbox-genome-wide-crispr-arrayed-libraries
#19
Emmanouil Metzakopian, Alex Strong, Vivek Iyer, Alex Hodgkins, Konstantinos Tzelepis, Liliana Antunes, Mathias J Friedrich, Qiaohua Kang, Teresa Davidson, Jacob Lamberth, Christina Hoffmann, Gregory D Davis, George S Vassiliou, William C Skarnes, Allan Bradley
CRISPR-Cas9 technology has accelerated biological research becoming routine for many laboratories. It is rapidly replacing conventional gene editing techniques and has high utility for both genome-wide and gene-focussed applications. Here we present the first individually cloned CRISPR-Cas9 genome wide arrayed sgRNA libraries covering 17,166 human and 20,430 mouse genes at a complexity of 34,332 sgRNAs for human and 40,860 sgRNAs for the mouse genome. For flexibility in generating stable cell lines the sgRNAs have been cloned in a lentivirus backbone containing PiggyBac transposase recognition elements together with fluorescent and drug selection markers...
May 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28533516/asd-restricted-and-repetitive-behaviors-associated-at-17q21-33-genes-prioritized-by-expression-in-fetal-brains
#20
R M Cantor, L Navarro, H Won, R L Walker, J K Lowe, D H Geschwind
Autism spectrum disorder (ASD) is a behaviorally defined condition that manifests in infancy or early childhood as deficits in communication skills and social interactions. Often, restricted and repetitive behaviors (RRBs) accompany this disorder. ASD is polygenic and genetically complex, so we hypothesized that focusing analyses on intermediate core component phenotypes, such as RRBs, can reduce genetic heterogeneity and improve statistical power. Applying this approach, we mined Caucasian genome-wide association studies (GWAS) data from two of the largest ASD family cohorts, the Autism Genetics Resource Exchange and Autism Genome Project (AGP)...
May 23, 2017: Molecular Psychiatry
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